| Autor: |
Wang N; Division of Immunology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United States., Yigit B; Division of Immunology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United States., van der Poel CE; Program in Cellular and Molecular Medicine, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States., Cuenca M; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States., Carroll MC; Program in Cellular and Molecular Medicine, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States., Herzog RW; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States., Engel P; Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona, Barcelona, Spain., Terhorst C; Division of Immunology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United States. |
| Abstrakt: |
Absence of the mouse cell surface receptor SLAMF3 in SLAMF3-/- mice suggested that this receptor negatively regulates B cell homeostasis by modulating activation thresholds of B cell subsets. Here, we examine whether anti-SLAMF3 affects both B and T cell subsets during immune responses to haptenated ovalbumin [NP-OVA] and in the setting of chronic graft vs. host disease (cGVHD) induced by transferring B6.C- H2 bm 12 /KhEg (bm12) CD4 + T cells into B6 WT mice. We find that administering αSLAMF3 to NP-OVA immunized B6 mice primarily impairs antibody responses and Germinal center B cell [GC B] numbers, whilst CXCR5 + , PD-1 + , and ICOS + T follicular helper (TFH) cells are not significantly affected. By contrast, administering αSLAMF3 markedly enhanced autoantibody production upon induction of cGVHD by the transfer of bm12 CD4 + T cells into B6 recipients. Surprisingly, αSLAMF3 accelerated both the differentiation of GC B and donor-derived TFH cells initiated by cGVHD. The latter appeared to be induced by decreased numbers of donor-derived Treg and T follicular regulatory (TFR) cells. Collectively, these data show that control of anti-SLAMF3-induced signaling is requisite to prevent autoantibody responses during cGVHD, but reduces responses to foreign antigens. |
